Interview: The Allergy Buster

Allergist Kari Nadeau ’88 is leading a daring medical study that aims to retrain the immune systems of children with severe food allergies.

A drop of milk. Traces of peanuts in a granola bar. Egg white swirled into a dessert. For 15 million Americans, including 1 in 13 kids, the smallest bite of certain everyday foods can trigger anything from itchy hives to life-threatening anaphylactic shock.

Fueled by a hypersensitive immune system that mistakes harmless food proteins for dangerous invaders, food allergies are as puzzling as they are perilous. Researchers are only beginning to understand why rates climbed 18% in a decade and continue to rise—or why 30% of kids have multiple food allergies. And while allergists routinely administer shots to calm hay fever and other respiratory allergies, there’s no cure or approved therapy for food allergies.

That may be changing. Daring research led by Kari Nadeau ’88, M.D., Ph.D., associate professor of allergies and immunology at Stanford University School of Medicine and Lucile Packard Children’s Hospital, holds promise for testing future treatment. Nadeau’s team launched the trials of “multi oral immunotherapy”—gradually increasing doses of allergenic foods for multiple food allergies—in January 2012. The research aims to retrain the immune systems of 85 children and adults who have allergies to as many as five foods. One group also received the allergy medicine Xolair to reduce risk for reactions and allow a faster increase of doses and a faster response.

The studies are ongoing, but this spring, a New York Times Magazine article that dubbed Nadeau “The Allergy Buster” reported on three young volunteers: Two could now eat normal portions of foods like eggs, milk, wheat, peanuts and almonds —and celebrated with pizza and cake. The third no longer had to avoid foods that might contain traces of food allergens, an important milestone. All must continue receiving doses of allergenic foods daily. Nadeau stresses that the treatment is experimental, with years of research still ahead. But the news made headlines around the world, galvanizing food-allergy sufferers and families hungry for help.

SARI HARRAR: What inspired you to focus your research on severe and multiple food allergies?

KARI NADEAU: Growing up, I had terrible allergies to molds and very bad asthma. I felt completely tethered to medicines and my inhaler. I grew out of them eventually, thank goodness, and moving from North Plainfield, N.J., to the bucolic setting at Haverford helped, too. I wondered why allergies develop and why only some kids grow out of them. At Haverford, you learn this great ability to interact with others and to ask the right questions. And I had amazing training in immunology with Judy Owen, molecular biology with Mel Santer, and biochemistry with Ariel Loewy that’s the foundation of my research skills. After medical school, I did postdoctoral work in immunology just as food allergies were increasing—doubling every 10 years. And as a pediatrician, half of the kids I saw in the clinic were having terrible food allergies, often with severe and nearly fatal consequences. I wanted to find out why food allergies were on the rise, how to better diagnose them, and how to treat them.

KN: It’s not that a too-clean environment by itself skews the immune system. We think there are other factors, too. Genetics play an important role, and on top of that, a process called epigenetics seems to be modifying DNA—turning genes on and off in ways that raise risk of allergies. We’ve found epigenetic changes in DNA in children exposed to ambient air pollution and to tobacco smoke. Research suggests that these changes may be passed along to future generations. A grandmother’s or grandfather’s exposures could raise a grandchild’s risk. How you stop that cycle, we don’t yet know.

SH: Your new studies give volunteers tiny doses of foods that, in many cases, nearly killed them in the past. Were you ever scared?

KN: We designed the treatment protocols very carefully. Experimental oral immunotherapy treatments with increasing doses of a single food—called monotherapy—had already been conducted, so we built on that. We worked closely with the FDA and other researchers to set up safeguards. We had to be sure that introducing several allergenic foods at once wouldn’t cause interactions. The total dose volunteers receive is the same as in monotherapy, but because they’re getting up to five foods, the dose of each individual food is just one-fifth as much, for example. When it’s time to increase the dose, volunteers come to the hospital and stay for several hours so that doctors and trained staff are on hand in case there’s a reaction. We’ll also reduce a dose if a child has a cold, for example, to reduce the risk for a reaction.

SH: How did families weigh the risks and benefits? Was it difficult recruiting volunteers?

KN: We have about 85 kids and adults in our two Phase 1 studies. There are another 800 people on a waiting list for future studies. The families and the volunteers are the real heroes—any therapy for food allergy is experimental, risky, and might not work long term. The families have already been living a life of avoiding food allergens and had to learn how to give their kids their doses at home during the oral immunotherapy trial. That takes a lot of bravery and commitment. There are also lots of safeguards built into the study. The families must already know how to use an EpiPen, and they receive re-education throughout the study. [Injected adrenaline stops anaphylactic shock, the potentially fatal allergic reaction that can make the windpipe swell shut and the heart fail.] Participants were asked not to exercise or do anything that increases body temperature or circulation for two hours after a dose, to reduce risk of a severe reaction. We followed up with families by phone frequently. And we’re always available. Our team is on call 24 hours a day, with a rotation schedule. It’s our responsibility. We want to answer questions and know what’s happening at all times.

SH: How does it feel when kids reach an important milestone—such as no longer avoiding foods that might contain allergen traces or being able to eat cake, pizza or peanut butter?

KN: Since our studies are still under way, I can’t comment on results. The three families interviewed for the New York Times Magazine story did see remarkable changes, and the staff has celebrated at the hospital with those who were finally able to have everyday foods without fear. Of course, maintenance is crucial. This isn’t a cure. Once volunteers reach full doses of allergenic foods, they must continue having them every day so that their immune system doesn’t become sensitized again. That’s 4,000 to 6,000 milligrams—about 2 pieces of bread, half an egg, half a cup of milk, or a half-tablespoon of peanut butter. That means big diet changes and a lot of work for parents. Ultimately, we’d like to find out whether that daily dose can be reduced while keeping immune-system cells, called T cells, nonallergenic.

SH: When might this therapy be available in doctor’s offices?

KN: If all goes well with future research, a treatment could be available in about 10 years. There’s reason to hope. Given some of the promising findings from these Phase 1 studies and other studies around the world, the next step could be a large, randomized study at several centers looking at safety and effectiveness in larger groups of people. We have several centers interested in participating and several companies interested in the project. We need resources. We need to lobby our Congress for more federal funding for food-allergy research and also promote financial support from private foundations and individuals as well.

SH: For now, what can parents of kids with food allergies—and adults with food allergies— do?

KN: It is important to understand that this food allergy therapy can only be conducted in research settings. No one should ever try this at home or with the help of a doctor outside of a research study. One option is to consider joining a study. Learn more by searching for food allergy treatment trials at http://clinicaltrials.gov. And it’s important to stay safe by working with an allergist so that you know how to avoid allergens, recognize allergic reactions quickly and how to use epinephrine promptly.

SH: Financing these studies was a big challenge; you were turned down for traditional research grants. How did grassroots philanthropy fill the gap?

KN: Clinical trials are costly. Through community events, the money was raised. I worked through the Stanford development office, giving talks. A group of parents of children with food allergies worked jointly with the development office at Stanford’s Lucile Packard Children’s Hospital to raise money—first as the Fund for Food Allergy Research at Stanford and then as the Stanford Alliance for Food Allergy Research Community Council. The brothers and sisters of kids with food allergies even held car washes and bake sales. It took lots of work, by lots of people.